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Acinetobacter baumannii nosocomial pneumonia: Is the outcome more

favorable in non-ventilated than ventilated patients?

Article  in  BMC Infectious Diseases · March 2013

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Yang et al. BMC Infectious Diseases 2013, 13:142
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RESEARCH ARTICLE Open Access

Acinetobacter baumannii nosocomial pneumonia:

is the outcome more favorable in non-ventilated
than ventilated patients?
Ya-Sung Yang1, Yi-Tzu Lee2,3, Tsai-Wang Huang4, Jun-Ren Sun5, Shu-Chen Kuo2,6, Chin-Hsuan Yang1, Te-Li Chen2*,
Jung-Chung Lin1, Chang-Phone Fung2 and Feng-Yee Chang7

Abstract
Background: Acinetobacter baumannii hospital-acquired pneumonia (HAP) is associated with a high mortality
worldwide. Non-ventilated patients with HAP (NVHAP) caused by nosocomial pathogens are reported to have a
more favorable outcome than those with ventilator-associated pneumonia (VAP). The current study was designed
to determine whether bacteremic patients with A. baumannii NVHAP also have a lower mortality than those
receiving assisted ventilation.
Methods: This retrospective 10-year study was conducted at a 2900-bed teaching hospital located in Northern
Taiwan. The population consisted of 144 patients with A. baumannii bacteremia and HAP. Of these 96 had VAP and
48 had NVHAP. Charts were reviewed for demographic characteristics, comorbidities, clinical manifestations,
antimicrobial susceptibility, and 14-day mortality. Clonal relationships were determined by molecular typing.
Results: There were no significant differences between the two groups in comorbidities (Charlson scores). Patients with
NVHAP were more likely to have developed bacteremia earlier, outside the ICU and undergone fewer invasive
procedures. They had significantly lower APACHE II scores, fewer bilateral pneumonias and lower rates of antimicrobial
resistance. No specific clones were identified in either group. The unadjusted (crude) 14-day mortality rates were not
significantly different between the groups (NVHAP 43.8% vs. VAP 31.3%, p = 0.196). The adjusted 14-day mortality risk was
significantly lower in ventilator-assisted patients (odds ratio = 0.201; 95% confidence interval = 0.075-0.538; p = 0.001).
Conclusions: Patients with bacteremic NVHAP and VAP caused by A. baumannii had similar crude mortality rates, but on
logistic regression analysis those receiving ventilator assistance had a significantly lower mortality. This may have been
due to better airway protection, more intensive monitoring with earlier diagnosis and treatment in patients with VAP,
greater innate susceptibility to infection in those with NVHAP and differences in the virulence of A. baumannii.
Keywords: Acinectobacter baumannii, Pneumonia, Hospital acquired, Ventilator

Background increasing among patients in intensive care units (ICUs)

The three most clinically relevant, but phenotypically undif-
ferentiated Acinetobacter species, Acinetobacter baumannii,
Acinetobacter nosocomialis (formerly Acinetobacter gen-
omic species 13TU), and Acinetobacter pittii (formerly
Acinetobacter genomic species 3), have emerged as import-
ant nosocomial pathogens [1]. The prevalence of health
care associated infections caused by Acinetobacter is
* Correspondence: tecklayyy@gmail.com
2
Institute of Clinical Medicine, School of Medicine, National Yang-Ming
University, Taipei, Taiwan
Full list of author information is available at the end of the article
and immunocompromised hosts [2-5]. The most common
clinical condition associated with these microorganisms is
hospital-acquired pneumonia (HAP), particularly for pa-
tients receiving mechanical ventilator assistance [6].
Among the three Acinetobacter species, A. baumannii is
associated with a poorer outcome and higher rates of anti-
microbial resistance [7]. Several A. baumannii virulence
factors have been identified. These include CsuA/BABCDE,
a chaperone-usher pili assembly system, the siderophore-
mediated iron acquisition system and outer membrane pro-
tein A (OmpA) [8,9]. The mortality rates for bacteremia

© 2013 Yang et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
Yang et al. BMC Infectious Diseases 2013, 13:142
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caused by A. baumannii range from 29.8 to 58.6%
[7,10,11]. It has been previously reported that non-
ventilated patients with HAP (NVHAP) caused by nosoco-
mial pathogens have a better outcome than those with
ventilator-associated pneumonia (VAP) [12-14]. It is not
known whether this applies to A. baumannii as well. The
current retrospective study was designed to determine
whether patients with A. baumannii bacteremic NVHAP
have a better outcome than those with bacteremic VAP.
Methods
Study population
This study was conducted at Taipei Veterans General
Hospital (T-VGH) during a ten-year period from January
2000 to December 2009. T-VGH is a 2900-bed tertiary-care
teaching hospital located in Taipei, Taiwan. The data were
analyzed at the Tri-Service General Hospital (TSGH),
National Defense Medical Center in Taipei, Taiwan.
Charts were reviewed for all patients with at least one
positive blood culture for A. baumannii who had symp-
toms and signs of infection. The inclusion criteria for
A. baumannii pneumonia [15] consisted of: a) at least one
positive respiratory sample (sputum, endotracheal aspirate,
or broncho-alveolar lavage [BAL]) for A. baumannii
obtained within 48 hours before or after the first positive
blood culture; b) a clinical course compatible with pneumo-
nia, including symptoms of acute respiratory infection and
acute infiltrates on a chest radiograph; and c) the positive
blood culture could not be attributed to another source of
infection. NVHAP was defined as pneumonia that occurred
48 hours or more after admission in non-ventilated pa-
tients. VAP was defined according to the 2005 American
Thoracic Society/Infectious Diseases Society of America
(ATS/IDSA) guidelines [16] as pneumonia that occurred
more than 48 hours after endotracheal intubation. The
quantitative microbiologic criteria for the diagnosis of HAP
required a bacterial count exceeding a threshold of 103 cfu/
mL in a protected specimen brushing, 104 or 105 cfu/mL in
a BAL fluid specimen or 106 cfu/mL in an endotracheal as-
pirate [16]. Patients <18 years of age and those with incom-
plete medical records were excluded. All the clinical
samples were taken as part of standard care. The standards
of patient care did not significantly change during the study
period. Mechanical ventilated patients not admitted to an
ICU were treated in a respiratory care center, respiratory
ward or common ward. The protocol was approved by the
T-VGH and TSGH Institutional Review Board (approval
number: 2011-10-012IC and 2-101-05-074) with a waiver
for informed consent.
Data Collection
Medical records were reviewed to extract clinical informa-
tion, including demographic characteristics, underlying
diseases, Charlson comorbidity score [17], duration of stay
Page 2 of 8
in an ICU, hospital stay, administration of individual anti-
microbials, the presence of a ventilator, central venous
catheters, a nasogastric tube, or a foley catheter at the time
of onset of bacteremia.
Chronic lung diseases other than chronic obstructive pul-
monary disease (non-COPD chronic lung disease) included
asthma, bronchiectasis, pulmonary fibrosis, and chronic
pulmonary tuberculosis. Immunosuppressive therapy was
defined as receipt of cytotoxic agents within 6 weeks, corti-
costeroids at a dosage equivalent to or higher than 10 mg
of prednisolone daily for more than 5 days within 4 weeks,
or other immunosuppressive agents within 2 weeks prior to
the onset of bacteremia. Neutropenia was defined as an
absolute neutrophil count <0.5×109 neutrophils/L. Recent
surgery was defined as operations performed within 4 weeks
prior to the onset of bacteremia. Chronic kidney disease
was defined as an estimated glomerular filtration rate <60
mL/min/1.73 m2 for at least 3 months prior to admission.
The severity of illness was evaluated using the acute physi-
ology and chronic health evaluation II (APACHE II) score
[18] within 24 hours prior to bacteremia onset.
Antimicrobial therapy was mainly based on the ATS/
IDSA guidelines (combined with the clinical judgment of
individual primary care physicians) [16]. Appropriate anti-
microbial therapy was defined as administration of at least
one antimicrobial agent, to which the causative pathogen
was susceptible, within 48 hours after the onset of
bacteremia, with an approved route and dosage for end
organ function. Antimicrobial therapy that did not
meet this definition was considered as inappropriate.
Monotherapy with an aminoglycoside was not considered
to be appropriate therapy. The primary outcome measure
was all-cause 14-day mortality following the onset
of bacteremia.
Microbiological Studies
Only the first blood culture from patients with two or more
positive blood cultures was included in the analysis. The
presumptive identification of the isolates to the level of
A. baumannii was performed with the API ID 32 GN sys-
tem (bioMérieux, Marcy l’Etoile, France) or Vitek 2 system
(bioMérieux, Marcy l’Etoile, France). A multiplex-PCR
method was used to identify A. baumannii to the genomic
species level [19]. Antimicrobial susceptibilities were deter-
mined by the agar dilution method according to the Clin-
ical Laboratory Standards Institute (CLSI) [20]. Multidrug
resistance was defined as resistance to three or more of the
following classes of antimicrobial agents: anti-pseudomonal
cephalosporins, anti-pseudomonal carbapenems, ampicil-
lin/sulbactam, fluoroquinolones, and aminoglycosides [21].
Molecular typing
The clonal relationships of the clinical isolates were de-
termined by pulsed-field gel electrophoresis (PFGE).
Yang et al. BMC Infectious Diseases 2013, 13:142
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PFGE of ApaI-digested genomic DNA was performed using
the Bio-Rad CHEF-Mapper apparatus (Bio-Rad Laborator-
ies, Hercules, CA, USA). DNA restriction patterns were
interpreted according to the criteria of Tenover et al. [22]
and cluster analysis was performed using BioNumerics ver-
sion 5.0 (Applied Maths, Sint-Martens-Latem, Belgium)
and the unweighted pair-group method with arithmetic av-
erages (UPGMA). The Dice correlation coefficient was used
with a tolerance of 1% in order to analyze any similarities
between banding patterns. In brief, isolates showing more
than three DNA fragment differences and a similarity of
<80% following dendrogram analysis were considered to
represent different pulsotypes.
Statistical analysis
To assess differences, the chi-square test with Yate’s cor-
rection or Fisher’s exact test was used to compare the
discrete variables; the Student’s t-test or Mann–Whitney
rank sum test was used to analyze continuous variables.
Logistic regression models were used to explore independ-
ent risk factors for 14-day mortality. Univariate analyses
were performed separately for each of the risk factor vari-
ables to ascertain the odds ratio (OR) and 95% confidence
interval (CI). All biologically plausible variables with a
p value of ≤ 0.20 in the univariate analysis exhibited by at
least 10% of the patients were considered for inclusion in
the logistic regression model for the multivariate analysis.
A backward selection process was utilized. Time to mor-
tality was analyzed using Kaplan-Meier survival analysis.
A p value <0.05 was considered statistically significant. All
the analyses were processed with Statistical Package for
the Social Sciences (SPSS) software version 18.0 (SPSS,
Chicago, IL, USA).
Results
During the study period 357 patients were found to have
had at least one episode of A. baumannii bacteremia. We
excluded 209 patients with polymicrobial bacteremia (89
patients) and those with positive blood culture attributable
to another source of infection (120 patients). The final
population that met the criteria for entry into the study
consisted of 148 patients of A. baumannii bacteremic
pneumonia. Four patients were further excluded because
of incomplete medical records. Among 144 patients, 48
had NVHAP and 96 had VAP. In addition to the clinical
features and radiographic findings that were compatible
with diagnosis of pneumonia, 93 VAP patients had posi-
tive cultures from endotracheal aspirates, three from BAL,
and all NVHAP patients from sputum specimens.
The demographic and clinical characteristics of the
study patients are summarized in Table 1. Compared to
VAP patients, NVHAP patients acquired their infections
less frequently in an ICU, earlier after admission, re-
ceived intensive care for pneumonia less frequently and
Page 3 of 8
received fewer procedures. Nineteen NVHAP patients (12
acquired pneumonia in an ICU and 7 outside an ICU) who
received intensive care in an ICU had mechanical ventila-
tion. Comorbidities and laboratory parameters were similar
between 2 groups, except that NVHAP patients had re-
ceived a fewer recent surgical procedures.
The Charlson comorbidity scores on hospital admission
were similar for the two groups. Patients with NVHAP
had significantly lower APACHE II scores at bacteremia
onset and less often presented with bilateral lung involve-
ment on radiological examination at the time of onset of
bacteremia.
To determine the molecular epidemiology of the causa-
tive pathogens, 55 (38.2%) of the A. baumannii isolates
were randomly selected for PFGE analysis. PGFE revealed
37 different pulsotypes (A to AK, Figure 1). Among the pa-
tients with NVHAP, there were 19 isolates in 16 pulsotypes:
A (n = 1), I (n = 1), J (n = 1), K (n = 4), L (n = 1), O (n = 1),
T (n = 1), U (n = 1), V (n = 1), W (n = 1), X (n = 1), Z (n =
1), AB (n = 1), AD (n = 1), AG (n = 1), and AK (n = 1). In
VAP patients, there were 36 isolates in 26 pulsotypes:
B (n = 1), C (n = 1), D (n = 2), E (n = 1), F (n = 1), G (n =
2), H (n = 1), J (n = 1), K (n = 1), M (n = 1), N (n = 1), P
(n = 3), Q (n = 2), R (n = 1), S (n = 1), Y (n = 3), Z (n = 2),
AA (n = 2), AB (N = 1), AC (n = 1), AE (n = 1), AF (n = 1),
AG (n = 2), AH (n = 1), AI (n = 1), and AJ (n = 1).
The antimicrobial susceptibility profiles of the clinical
isolates of A. baumannii are shown in Table 2. Isolates
from NVHAP patients exhibited significantly lower rates
of resistance to all antimicrobials tested. The initial anti-
microbial agents used in both group are summarized in
Table 3. The selection of antimicrobial agents was similar
between both groups. Anti-pseudomonal carbapenems
were the most commonly used agents in both groups,
followed by anti-pseudomonal cephalosporins and penicil-
lins. More NVHAP than VAP patients received an appro-
priate antimicrobial therapy, but the differences were not
significant (41.7% vs. 29.2%, p = 0.189).
The 14-day mortality rate was slightly higher in NVHAP
patients than those with VAP (43.8% vs. 31.3%, p = 0.189),
despite the finding that patients with NVHAP had less
severe illness at the onset of bacteremia and received ap-
propriate antimicrobial therapy more often than patients
with VAP. Multivariate logistic regression analysis was
performed to identify potential independent risk or pro-
tective factors for 14-day mortality. Although ICU admis-
sion did not meet the criteria for entering multivariate
logistic regression analysis, it was included because of
its clinical importance. Patients with VAP caused by
A. baumannii had a significantly lower mortality than
those with NVHAP on regression analysis (odd ratio
[OR] = 0.201; 95% confidence interval [CI] = 0.075-0.538;
p = 0.001). Patients with higher APACHE II scores (OR =
1.164; 95% CI = 1.103-1.229; p <0.001), use of
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Table 1 Demographic and clinical characteristics of Table 1 Demographic and clinical characteristics of
patients with bacteremic hospital-acquired pneumonia patients with bacteremic hospital-acquired pneumonia
caused by Acinetobacter baumanniia caused by Acinetobacter baumanniia (Continued)
Demographic or Non-ventilator- Ventilator- Total parental nutrition 1 (2.1) 8 (8.3) 0.273
characteristic associated associated p
(n = 48) (n = 96) Tracheostomy 7 (14.6) 16 (16.7) 0.936
Value
n (% or IQRa) Shockd 29 (60.4) 58 (60.4) 1
Age in year 74 (54.8-81.8) 74 (59.0- 0.944 APACHE II scored 24 (17.3-31.8) 27 (21.3- 0.015
80.0) 34.8)
Gender, male 40 (83.3) 73 (76.0) 0.43 Radiological features
Acquired in ICU 12 (25.0) 84 (87.5) b
<0.001 Bilateral radiologic 27 (56.3) 81 (84.4) 0.001
c
involvement
ICU admission after 19 (39.6) 86 (89.6) <0.001
pneumonia Pleural effusion 20 (41.7) 32 (33.3) 0.425
Days of hospitalization prior to 14.5 (3.2-3.6) 22.5 (12.0- 0.021 Appropriate antimicrobial 20 (41.7) 28 (29.2) 0.189
bacteremia 40.8) therapy
Comorbidity Combination antimicrobial 4 (8.3) 7 (7.3) 1
therapy
Charlson comorbidity score 3 (2.0-5.0) 3 (2.0-5.0) 0.861
Outcome
Hypertension 22 (45.8) 47 (49.0) 0.86
14-day mortality 21 (43.8) 30 (31.3) 0.196
Coronary artery disease 14 (29.2) 15 (15.6) 0.091 a
Data are median value (interquartile range) for continuous variables and
Congestive heart failure 6 (12.5) 19 (19.8) 0.392 number of cases (%) for categorical variables. IQR = interquartile range;
ICU = intensive care unit; COPD = chronic obstructive pulmonary disease;
Cerebral vascular disease 7 (14.6) 27 (28.1) 0.111
APACHE = Acute Physiologic and Chronic Health Evaluation.
b
COPD 12 (25.0) 27 (28.1) 0.842 Other patients were cared in a respiratory care center, respiratory ward, or
common ward.
Non-COPD chronic lung 5 (10.4) 15 (15.6) 0.551 c
Twelve acquired pneumonia in an ICU and 7 outside an ICU, all of them
disease received mechanical ventilation after pneumonia.
d
At the time the blood culture was obtained.
Alcohol 3 (6.3) 13 (13.5) 0.302
Liver cirrhosis 4 (8.3) 5 (5.2) 0.481 corticosteroids (OR = 5.739; 95% CI = 2.002-16.454; p =
Chronic kidney disease 15 (31.3) 32 (33.3) 0.95 0.001) and solid malignancies (OR = 4.242; 95% CI =
Type 2 diabetes 10 (20.8) 35 (36.5) 0.086 1.554-11.578; p = 0.005) also had a significantly higher
14-day mortality regardless of the use of ventilators. ICU
Collagen vascular disease 4 (8.3) 7 (7.3) 1
admission was not found to be a protective factor for
Usage of 18 (37.5) 32 (33.3) 0.757
immunosuppressants
14-day mortality.
Usage of corticosteroids 7(14.6) 23 (24.0) 0.276
Discussion
Neutropenia 4 (8.3) 7 (7.3) 1 In this study, we found that patients with A. baumannii
Malignancy 22 (45.8) 28 (29.2) 0.073 bacteremia with NVHAP or VAP had similar demographic
Hematologic 7 (14.6) 6 (6.3) 0.125 characteristics and Charlson comorbidity scores at hos-
malignancy pital admission. Patients with NVHAP differed from VAP
Solid malignancy 17 (35.4) 23 (24.0) 0.211 in that fewer acquired their infections in an ICU and they
Previous shock 8 (16.7) 27 (28.1) 0.192 developed pneumonia sooner after admission. They re-
Recent surgery 8 (16.7) 34 (35.4) 0.032 ceived intensive care for pneumonia less often and had
fewer invasive and surgical procedures. Patients with
Trauma 0 (0) 4 (4.2) 0.301
NVHAP also had lower APACHE II scores at the onset of
Proceduresd
bacteremia. They presented with bilateral lung involve-
Abdominal drain 1 (2.1) 5 (5.2) 0.658 ment less often and had fewer antimicrobial resistant
Arterial line 5 (10.4) 36 (37.5) 0.001 strains. The crude 14-day mortality rate was slightly higher
Central venous catheter 22 (45.8) 71 (74.0) 0.002 in NVHAP patients than those with VAP. Following ad-
Pulmonary artery catheter 6 (12.5) 20 (20.8) 0.319 justment for multiple risk factors by logistic regression
analysis, patients with VAP had lower 14-day mortality
Foley catheter 28 (58.3) 78 (81.3) 0.006
than those with NVHAP.
Hemodialysis 4 (8.3) 10 (10.4) 0.774
The findings on regression analysis appear to be
Nasogastric tube 35 (72.9) 93 (96.9) <0.001 counter-intuitive since patients with NVHAP were less ill
Thoracic drain 0 (0) 7 (7.3) 0.095 and did not appear to require use of a ventilator. They
would not be expected to be better off if treated with a
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Figure 1 Pulsed-field gel electrophoresis of 55 representative strains of Acinetobacter baumannii from patients with bacteremic
nosocomial pneumonia. NVHAP = non-ventilated hospital-acquired pneumonia; VAP = ventilator-associated pneumonia.
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Table 2 Comparison of antimicrobial susceptibilities of blood isolates in patients with non-ventilator and ventilator-
associated hospital-acquired pneumonia
Resistance, n (%)
Antimicrobial agent Non-ventilator associated (n = 48) Ventilator-associated (n = 96) p Value
Amikacin 27 (56.3) 86 (89.6) <0.001
Gentamicin 32 (68.1) 88 (93.6) <0.001
Ceftazidime 30 (63.8) 93 (96.9) <0.001
Cefepime 22 (45.8) 73 (76.0) 0.001
Piperacillin/tazobactam 25 (52.1) 77 (80.2) 0.001
Ampicillin/sulbactam 17 (36.2) 62 (65.3) 0.002
Ciprofloxacin 33 (68.8) 93 (96.9) <0.001
Imipenem 13 (27.1) 47 (49.0) 0.020
Multidrug resistancea 31 (64.6) 94 (97.9) <0.001
a
Definition: resistance to three or more of the following classes of antimicrobial agents: anti-pseudomonal cephalosporins, anti-pseudomonal carbapenems,
ampicillin/sulbactam, fluoroquinolones, and aminoglycosides.

ventilator, but this remains a possibility since it is difficult
to assess individual clinical decisions in critically ill pa-
tients. It is reasonable to suppose that since most VAP pa-
tients were managed in ICUs, ventilator use may have
been a surrogate marker for better and more intensive
care. The upper airways of ventilated patients are better
protected from contaminated secretions and their sputum
is more readily expectorated [23,24]. The VAP patients
might have been diagnosed and received antimicrobial
therapy earlier.
Prompt use of appropriate antibiotics is essential to
optimize the outcome of HAP [25-27]. A recent study
showed that appropriate antimicrobial therapy reduced the
mortality of bacteremic A. baumannii infections [11]. In
the current study the isolates from patients with VAP were
more likely than those with NVHAP to be resistant to
multiple antimicrobial agents. This probably accounted for
the tendency for less patients with VAP to receive appropri-
ate therapy. Nevertheless, the frequency of antimicrobial
resistance and inappropriate treatment was high in both
groups. This finding is not surprising since A. baumannii is
often resistant to the antimicrobial agents used for empir-
ical therapy of patients with HAP. Routine respiratory sur-
veillance cultures might be helpful to guide the selection of
the most appropriate empirical therapy [28,29]. This should
be particularly useful in institutions where multidrug resist-
ant pathogens are endemic. The antimicrobial susceptibility
of 1,160 strains of Acinetobacter species isolated during a
10-year nationwide survey in Taiwan was recently reported
[30]. The overall susceptibility to tigecycline and colistin
was 97.7% and 99.8%, respectively. The susceptibility of
carbapenem resistant isolates to these drugs was 98.1% and
100% respectively [30]. More prompt use of these anti-
microbial agents should improve use of appropriate anti-
microbial therapy. These drugs were not available at our
hospital during the study period.
It is also possible that there were important differences
in the pathogenicity of the invading microorganism in the

Table 3 Comparison of initial antimicrobial agents use in patients with non-ventilator and ventilator-associated
hospital-acquired pneumonia
Main agents used Group, n (%) p
Value
Non-ventilator associated (n = 48) Ventilator-associated (n = 96)
Anti-pseudomonal penicillinsa 5 (10.4) 10 (10.4) 1.000
Anti-pseudomonal cephalosporinsb 12 (25.0) 18 (18.8) 0.514
c
Anti-pseudomonal fluoroquinolones 4 (8.3) 4 (4.2) 0.441
Anti-pseudomonal carbapenemsd 14 (29.2) 29 (30.2) 1.000
Ampicillin/sulbactam or sulbactam 5 (10.4) 13 (13.5) 0.789
Non-anti-pseudomonal β-lactamasee 6 (12.5) 16 (16.7) 0.682
Miscellaneousf 2 (4.2) 6 (6.3) 0.719
a
Including piperacillin, piperacillin/tazobactam, and ticarcillin/clavulanate.
b
Including cefoperazone, ceftazidime, cefepime, and cefpirome.
c
Including ciprofloxacin and levofloxacin.
d
Including imipenem and meropenem.
e
Including penicillin, amoxicillin/clavulanate, cefazolin, cefuroxime, cefotaxime, cefmetazole, and flomoxef.
f
Including teicoplanin or clindamycin plus amikacin.
Yang et al. BMC Infectious Diseases 2013, 13:142
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NVHAP and VAP populations. This concept is based on
the higher frequency of antibiotic resistant strains among
patients with VAP. It has been shown that the survival fit-
ness and virulence of bacteria are often compromised in
isolates with multidrug resistance [31,32]. PFGE analysis
did not reveal a specific epidemic clone of A. baumannii
among the two groups, but we cannot exclude the possi-
bility that patients with VAP were infected by less invasive
or less virulent clones. Another possible explanation is
that patients with NVHAP may have been more suscep-
tible to infection with A. baumannii than those with VAP
because they developed bacteremic pneumonia without
the need for intubation and mechanical respiration.
The APACHE II score at the onset of A. baumannii
bacteremia has been shown to be a reliable parameter
for predicting mortality [33]. In the current study we
found that APACHE II score to be an independent risk fac-
tor for mortality in patients with A. baumannii HAP. In
addition, solid malignancies and usage of corticosteroids
were identified as independent risk factors for mortality in
this study. The proportion of malignancies was higher in
NVHAP patients (46% vs. 29%), though there was no sig-
nificant difference between the two groups, but following
regression analysis, solid malignancies was an independent
risk factor for mortality. The higher proportion of malig-
nancies may also play a role in the poorer outcome of
NVHAP patients. The findings posed important informa-
tion in risk stratification for A. baumannii HAP.
This is the first study specifically designed to compare the
outcome of NVHAP and VAP bacteremic A. baumannii
pneumonia. The strengths of this study are the relatively
large number of patients managed in a major tertiary care
teaching hospital using well defined criteria for underlying
diseases, examination of clonal relationships and a clear
14-day end-point. The limitations include the difficulty to
differentiate colonization from infection in sputum cultures
of patients with HAP. To improve the specificity of the
quantitative sputum cultures we excluded patients with
A. baumannii bacteremia that could not be attributed to
pneumonia. Concomitant catheter related bacteremia or
secondary catheter infection could not be completely ex-
cluded because central venous catheter cultures were un-
available. Because of the retrospective design we were
unable to control the selection of the antimicrobial agents
prescribed by the hospital staff. However, there were no sig-
nificant differences between the VAP and NVHAP in
respect to the choice of drugs and variety of antimicrobial
regimens that might have affected the clinical outcomes.
Conclusions
Patients with bacteremic NVHAP and VAP caused by
A. baumannii had similar crude mortality rates, but on
logistic regression analysis those receiving ventilator
assistance had a significantly lower mortality. This may
Page 7 of 8
have been due to better airway protection, more inten-
sive monitoring with earlier diagnosis and treatment in
patients with VAP, greater innate susceptibility to infec-
tion in those with NVHAP and differences in the
virulence of A. baumannii.
Abbreviations
A. baumannii: Acinetobacter baumannii; APACHE II: Acute Physiology And
Chronic Health Evaluation II; ATS/IDSA: American Thoracic Society/Infectious
Diseases Society of America; BAL: Broncho-alveolar lavage; CI: Confidence
interval; CLSI: Clinical Laboratory Standards Institute; COPD: Chronic obstructive
pulmonary disease; DNA: Deoxyribonucleic acid; HAP: Hospital-acquired
pneumonia; ICU: Intensive care unit; NVHAP: Non-ventilated HAP; OmpA: Outer
membrane protein A; OR: Odds ratio; PCR: Polymerase chain reaction;
PFGE: Pulsed-field gel electrophoresis; SPSS: Statistical Package for the Social
Sciences; TSGH: Tri-Service General Hospital; T-VGH: Taipei Veterans General
Hospital; UPGMA: Unweighted pair-group method with arithmetic averages;
VAP: Ventilator-associated pneumonia.
Competing interests
Te-Li Chen is a medical advisor of TTY Biopharm. Other authors declare that
they have no competing interests.
Authors’ contributions
YSY, YTL and TLC participated in the study design, analysis of data, and
writing of the manuscript. JRS and SCK participated in data collection. TWH
and CHY participated in analysis of data. JCL, CPF and FYC revised the
manuscript with important intellectual contribution. All authors read and
approved the final manuscript.
Acknowledgements
The authors wish to express their appreciation to Calvin M. Kunin for his
critical review of this manuscript.
This study was supported by grants from the Tri-Service General Hospital
(TSGH-C100-103, TSGH-C102-113, MAB101-03 and MAB102-13),the Taipei
Veterans General Hospital (V101E4-003, V101A-017, and V101C-021), the
National Science Council (101-2314-B-010-027-MY3), and the National Health
Research Institute (IV-101-PP-12).
Author details
1
Division of Infectious Diseases and Tropical Medicine, Department of
Internal Medicine, Tri-Service General Hospital, National Defense Medical
Center, Taipei, Taiwan. 2Institute of Clinical Medicine, School of Medicine,
National Yang-Ming University, Taipei, Taiwan. 3Emergency Department,
Taipei Veterans General Hospital, Taipei, Taiwan. 4Division of Thoracic
Surgery, Department of Surgery, Tri-Service General Hospital, National
Defense Medical Center, Taipei, Taiwan. 5Clinical Microbiology Laboratory
Division of Clinical Pathology, Tri-Service General Hospital, National Defense
Medical Center, Taipei, Taiwan. 6National Institute of Infectious Diseases and
Vaccinology, National Health Research Institutes, Miaoli County, Taiwan.
7
Department of Health, Centers for Disease Control, Taipei, Taiwan.
Received: 20 November 2012 Accepted: 12 March 2013
Published: 19 March 2013
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